Ultrastructural Observation Of Secretory Cells In Intestinal Mucosa Of Inflammatory Bowel Disease

BackgroundInflammatory bowel disease(IBD)is a chronic inflammatory disease of the intestine,including two main clinical types:Crohn’s disease(CD)and ulcerative colitis(UC).In the past 20 years,the incidence of IBD in the Asian population has shown a significant upward trend.The defect of intestinal epithelial barrier function in IBD has been confirmed.The intestinal epithelial barrier function is mainly completed by the epithelial layer,lamina propria and muscularis mucosae.Goblet cells(GC),Paneth cells(PC)and intestinal Enteroendocrine Cells(EECs),as the main secretory cells,play an important role in maintaining the stability of the epithelial barrier in IBD patients.In addition,more and more studies have shown that EECs play an important role in the neuro-endocrine-immunoregulation axis,and also play an important role in the pathogenesis of IBD.Therefore,this study will enroll clinical IBD patients and 2,4,6-trinitrobenzenesulfonic acid(TNBS)and dextran sodium sulfate(DSS)-induced IBD model mice,to describe the ultrastructural changes of secretory cells in intestinal mucosa of IBD patients and enteritis mice.AimTo observe the ultrastructural changes of intestinal mucosal secretory cells in patients with inflammatory bowel disease and enteritis model mice,mainly including neuroendocrine cells,Paneth cells and goblet cells,and to explain their role in the pathogenesis of IBD from an ultrastructural point of view.MethodsBiopsy forceps were used to obtain 10 colon specimens from UC patients and healthy control group,and 10 small intestine specimens from CD patients and healthy control group.18 male C57BL/6J mice were divided into wild group,TNBS group,and DSS group.Using 2,4,6-trinitrobenzenesulfonic acid to obtain the acute-phase colitis mouse model,using dextran sodium sulfate to obtain the acute-phase colitis mouse model,6 pieces of colon specimens were collected from both wild mice and TNBS model group mice.Six cases of colon specimens and 6 cases of small intestine specimens were obtained from DSS model group mice.The ultrastructural changes of secretory cells in the inflammatory state were investigated by transmission electron microscope(TEM),and the number of EECs was compared between above groups by immunohistochemistry.ResultsCompared with the healthy control group,the colonic goblet cell muxogen granules in ulcerative colitis patients were significantly destroyed;compared with the wild mice group,the colonic goblet cell muxogen granules in the DSS group and TNBS group were significantly destroyed.The numbers of colonic serotonin(5-Hydroxytryptamine,5-HT)and chromogranin A(CgA)immunoreactive positive cells of the mice in the DSS group were increased compared with those in the wild mice group.The number of 5-HT immunoreactive positive cells of the mice in the TNBS group was increased compared with wild mice,while the number of chromogranin A immunoreactive cells decreased.Compared with UC patients and CD patients in healthy control group,and compared with DSS group and TNBS group in wild mice,the damage degree of neuroendocrine cell organelles between each group was lower,and there was no significant difference.Autophagy-lysosomes are increased in small intestinal Paneth cells in patients with Crohn’s disease.Compared UC patients and CD patients with healthy control group,and compared DSS group and TNBS group with wild mice,the damage degree of neuroendocrine cell organelles among those groups demonstrated no significant difference.Autophagy-lysosomes are increased in small intestinal Paneth cells in patients with Crohn’s disease.ConclusionDSS mice,TNBS mice intestinal mucosal enterochromaffin cells proliferation,but no obvious ultrastructural changes.Muxogen granules in goblet cells in patients with ulcerative colitis,DSS model mice and TNBS model mice were more destroyed than those in the wild group,which could explain the increased secretion of intestinal mucus in patients with ulcerative colitis.Autophagy and lysosomes are increased in small intestinal Paneth cells in patients with Crohn’s disease.which may be related with Paneth cell autophagy deficiency.The changes in the ultrastructure of secretory cells of intestinal mucosa in patients with IBD may play an important role in the regulation of neuroimmunity.